ASCO 2023 Meeting Report — Hematologic Malignancies

The 2023 American Society of Clinical Oncology (ASCO) annual meeting, held June 2 to 6 in Chicago, highlighted important advances in treatment across a broad spectrum of hematologic malignancies. Here, Associate Editor Dr. Michael Williams reviews several key trials in myelodysplastic syndromes, Hodgkin lymphoma, and lymphocytic leukemia.

First-line treatment with luspatercept, compared with epoetin alfa, improves anemia and reduces need for red blood cell (RBC) transfusions in transfusion-dependent adults with lower-risk myelodysplastic syndromes (MDS), according to a planned interim analysis from the industry-sponsored, phase 3 COMMANDS trial (abstract 7003 and Lancet 2023 Jun 10; [e-pub]).

In the open-label, randomized trial, 354 patients who had not previously taken erythropoietin-stimulating agents received subcutaneous luspatercept (1 mg/kg titrated up to 1.75 mg/kg, once every 3 weeks) or epoetin alfa (450 IU/kg titrated up to 1050 IU/kg once per week) for at least 24 weeks; 301 patients were included in the interim analysis.

The primary endpoint — independence from RBC transfusion for 12 or more weeks plus a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks — was achieved by 59% of the luspatercept group versus 31% of the epoetin alfa group (P<0.0001). More patients in the luspatercept group achieved a hematologic improvement–erythroid response at or after 8 weeks (74% vs. 51% with epoetin alfa) and transfusion independence at 24 weeks (48% vs. 29%, respectively). Improvement was observed in patients with SF3B1 mutations and those with positive ringed sideroblast status, as well as other MDS subtypes.

Treatment-related adverse events occurred in 30% of the luspatercept group and 18% of the epoetin alfa group; 4.5% versus 2.3%, respectively, discontinued therapy due to an adverse event.

Summary by Cara Adler, Staff Writer

COMMENT — Dr. Michael E. Williams

Luspatercept, which enhances erythroid maturation, significantly outperformed epoetin alfa in patients with transfusion-dependent lower-risk MDS and provides an important new therapeutic option for these patients. This practice-changing study supports utilization of luspatercept prior to an erythrocyte-stimulating agent in this patient population.

Adding the PD-1 inhibitor nivolumab instead of brentuximab vedotin to front-line chemotherapy improves progression-free survival in children and adults with newly diagnosed stage 3 or 4 classic Hodgkin lymphoma, according to the second planned interim results of the industry-funded phase 3 Intergroup S1826 trial (abstract LBA4).

Nearly 1000 patients aged 12 and older were randomized to receive six cycles of nivolumab plus AVD (doxorubicin, vinblastine, dacarbazine) or brentuximab vedotin plus AVD. At 12 months, progression-free survival, the primary outcome, was significantly higher with nivolumab-AVD than with brentuximab vedotin–AVD (94% vs. 86%; hazard ratio, 0.48). This benefit was consistent across subgroups, including age, disease stage, International Prognostic Score, and presence or absence of B symptoms.

Grade 3 or 4 hematologic adverse events, including neutropenia, were more common with nivolumab (48% vs. 35%), while any-grade peripheral neuropathy was more frequent with brentuximab vedotin. The incidence of febrile neutropenia, sepsis, and infections was similar in the two arms. Treatment was discontinued by 11% of patients in the nivolumab arm compared with 22% in the brentuximab vedotin arm. Less than 1% of patients received radiation therapy.

Summary by Cara Adler, Staff Writer

COMMENT — Dr. Michael E. Williams

Pending longer follow-up and full publication of this landmark study, nivolumab-AVD is poised to become a new standard of care for advanced-stage Hodgkin lymphoma. While interim restaging PET/CT imaging was performed after cycle 2 of therapy, no risk-adapted dose-escalation or de-escalation modifications were made. Virtually all patients were spared the need for radiation therapy, thus reducing the risk of late second malignancy and cardiovascular events — an especially important finding in this largely adolescent and young adult population.

Watch our interview with the lead study author.

Treatment with the CD19-directed chimeric antigen-receptor T-cell (CAR-T cell) lisocabtagene maraleucel (liso-cel) yields high responses in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received two or more lines of therapy, according to a multicenter, industry-sponsored, phase 1/2 trial (abstract 7501 and Lancet 2023 Jun 6; [e-pub]).

Patients with CLL/SLL who progress after treatment with a Bruton's tyrosine kinase (BTK) inhibitor and the B-cell lymphoma 2 inhibitor venetoclax currently have limited therapeutic options and poor survival.

Liso-cel was administered after lymphodepleting chemotherapy at dose levels of either 50 or 100 × 10⁶ cells. Of 137 enrolled patients undergoing leukapheresis, 117 received liso-cel infusion. Patients had received a median of five prior lines of therapy; all had received a BTK inhibitor and 70 had also received venetoclax. The 49 patients treated at the higher dose level comprised the primary efficacy cohort; of these, 18% showed complete remission (CR) — significantly higher than historic controls. Overall, 47% of this cohort responded, with a median duration of response of 35.3 months (not reached for patients with CR).

Among all patients who received liso-cel, grade 3 cytokine release syndrome occurred in 9% and grade 3 neurologic events in 18%; one death was attributed to liso-cel.

COMMENT: Treatment of CLL/SLL that does not respond to multiple lines of therapy, including targeted agents and chemoimmunotherapy, remains an unmet need. Liso-cel therapy showed deep remissions and durable response in a subset of patients, which offers promise for this cellular therapeutic agent and for other CAR-T products or T-cell–engaging bispecific monoclonal antibodies.

Summary and comment by Dr. Michael E. Williams